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Objective To detect levels of interleukin?4(IL?4), IL?10, interferon?γ(INF?γ)and transforming growth factor?β(TGF?β)in the culture supernatant of peripheral blood mononuclear cells (PBMCs)from patients with atopic dermatitis(AD), and to evaluate regulatory effects of benvitimod on these cytokines. Methods PBMCs were isolated from 20 AD patients and 20 healthy controls. Then, PBMCs from AD patients were equally divided into 4 groups to be cultured with phosphate?buffered saline (PBS group), 400 nmol/L benvitimod solution (benvitimod group), 250 nmol/L dexamethasone solution (dexamethasone group) and 10 nmol/L tacrolimus solution (tacrolimus group), respectively. Enzyme?linked immunosorbent assay(ELISA)was performed to detect levels of IL?4, IL?10, INF?γand TGF?βin the culture supernatant of PBMCs. Results Compared with healthy controls, patients with AD showed significantly higher level of IL?4(83.4 ± 12.2 vs. 44.3 ± 5.7 pg/ml, P0.05). Compared with PBS, 400 nmol/L benvitimod could decrease the expression of IL?4(50.2 ± 10.1 vs. 83.3 ± 12.2 pg/ml, P 0.05)and INF?γ(9.56 ± 5.1 vs. 12.5 ± 2.3 pg/ml, P>0.05), but increase the expression of TGF?β(203.6 ± 15.3 vs. 178.9 ± 17.4 pg/ml, P>0.05)by PBMCs. In addition, no significant differences in the expression of IL?4, IL?10, INF?γ or TGF?β were observed between the benvitimod group and dexamethasone group or tacrolimus group(all P>0.05). Conclusion Benvitimod can regulate the expression of IL?4, IL?10, INF?γand TGF?βby PBMCs in patients with AD.
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Objective To evaluate the efficacy of benvitimod on allergic contact dermatitis (ACD) in a mouse model of allergic contact dermatitis.Methods Acute and chronic ACD models were established respectively in 42 BALB/c mice through 2,4-dinitrofluorobenzene (DNFB) sensitization and challenge.Then,the BALB/c mice were equally divided into 7 groups with 6 mice in every group:normal control group receiving no treatment,five treatment groups topically treated with 0.1％ dexamethasone solution,0.1％ tacrolimus (FK506) solution,0.5％ benvitimod solution,1.0％ benvitimod solution and 2.0 ％ benvitimod solution respectively,and dehydrated alcohol group treated with dehydrated alcohol only.All the drug solutions were topically applied at 24 and 36 hours after the last challenge in the murine models of acute ACD which were sacrificed at 48 hours,and twice daily from day 7 to 21 after the initial sensitization in the murine models of chronic ACD which were sacrificed on day 21 after the first topical treatment.Ear tissues were obtained from these mice and subjected to measurement of ear thickness and weight,as well as pathological examination and evaluation of inflammatory infiltrate by hematoxylin-eosin (HE) staining.The safety of these drugs was also estimated at the end of treatment.Results In the murine models of acute ACD,benvitimod showed no obvious therapeutic effect at 24 hours,with no significant differences in bilateral difference in ear thickness or weight between the three benvitimod groups and dehydrated alcohol group (all P ＞ 0.05).Meanwhile,in the murine models of chronic ACD,benvitimod markedly decreased the swelling degree of ears,with significant differences between the three benvitimod groups (0.5％,1.0％ and 2.0％) and dehydrated alcohol group in bilateral difference in ear thickness ((71.50 ± 3.15) × 10-3 mm,(75.50 ± 3.02) × 10-3 mm and (69.50 ± 2.59) × 10-3 mm vs.(91.83 ± 2.04) × 10-3 mm,all P＜ 0.01) and weight ((2.33 ± 0.45) mg,(2.30 ± 0.57) mg and (2.38 ± 0.27) mg vs.(3.73 ± 0.33) mg,all P ＜ 0.01) after 3 weeks of treatment.The inflammatory infiltration in ear tissue was significantly attenuated in murine models of both acute and chronic ACD by the three concentrations of benvitimod compared with dehydrated alcohol (all P ＜ 0.01).Conclusions Topical benvitimod can inhibit chronic ACD in mice induced by 2,4-DNFB,but exhibits no obvious effect on acute ACD.No apparent local adverse effects were observed during the treatment with benvitimod in these mice.
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OBJECTIVE: To evaluate the effects of the pH condition in which the plasma samples were prepared on the matrix effects of HPLC-MS/MS analysis of stilbene compounds.